Equipment supplement to "Training Innate Immunity: A new approach to the treatment of sepsis"

《训练先天免疫：治疗脓毒症的新方法》的设备补充

• 批准号: 10794766
• 负责人: EDWARD R SHERWOOD
• 金额: $ 13.63万
• 依托单位: EAST TENNESSEE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10794766
• 关键词: 20 year old; Antibiotic Resistance; Award; Candida albicans; Cause of Death; Chromatography; Equipment; Expenditure; FDA approved; Glucans; Hospitals; Immune; Immunity; Immunosuppressive Agents; Incidence; Innate Immune System; Intensive Care Units; Laboratories; Natural Immunity; Parents; Patients; Performance; Pharmaceutical Preparations; Phenotype; Prevention approach; Procedures; Process; Quality Control; Reagent; Research; Sepsis; Source; System; Training; aging population; beta-Glucans; cognitive disability; detector; effective therapy; experimental study; hospital readmission; novel; novel strategies; opportunistic pathogen; physically handicapped; prevent; recurrent infection; response; secondary infection; trend

Abstract Sepsis is the leading cause of death in non-cardiac intensive care units (ICU) and accounts for 40% of ICU expenditures. Patients that survive sepsis have long term physical and cognitive disabilities and are frequently readmitted to the hospital with recurrent infections. Over the past two decades there has been an increased incidence of sepsis and this trend is likely to continue due to our aging population, increased use of immunosuppressive drugs and invasive procedures and the emergence of antibiotic resistant opportunistic pathogens. Attempts at developing effective therapies to prevent or treat sepsis have proven to be exceedingly difficult. No drugs are currently approved by the FDA for the treatment of sepsis. It is clear that new approaches for the prevention and treatment of sepsis are needed. In the parent award (RO1GM119197), we proposed the novel concept that it is possible to “train” the innate immune system to facilitate a more effective response to existing and secondary infections. In this research, we utilize β-glucan isolated from C. albicans to induce trained immunity. The β-glucan reagent is prepared in the PIs (Williams) laboratory and it is the immune training reagent used for the experiments detailed in the parent award at both ETSU (Williams) and Vanderbilt (Sherwood). In fact, the Williams laboratory is the “sole source” of the β-glucan immune training reagent which is employed in the parent award. The isolation and quality control of β-glucan is a multi-step process, which requires chromatographic purification at the preparative level in order to obtain a high purity, i.e. >95%, β- glucan reagent in quantities sufficient for the experiments being done at both ETSU and Vanderbilt. Our current preparative chromatography system is twenty years old. It is currently not operational and must be replaced. This supplement requests an Agilent 1260 Infinity II preparative chromatography system. The Agilent 1260 system is a high performance, fully automated preparative chromatography system with multiple detectors that will enable us to isolate and purify sufficient quantities of -glucan in order to complete the specific aims of our parent award.

摘要 脓毒症是非心脏重症监护病房(ICU)的主要死亡原因，占ICU的40% 支出。在脓毒症中存活下来的患者有长期的身体和认知障碍，并且经常 因反复感染再次入院治疗。在过去的二十年里， 脓毒症的发病率和这一趋势可能会继续，因为我们的人口老龄化，增加使用 免疫抑制药物和侵入性手术以及抗生素耐药机会主义的出现 病原体。试图开发有效的治疗方法来预防或治疗败血症已被证明是非常有效的。 很难。FDA目前还没有批准用于治疗脓毒症的药物。很明显，新的 预防和治疗败血症的方法是必要的。在家长奖(RO1GM119197)中，我们 提出了新的概念，即有可能“训练”先天免疫系统，以促进更有效的 对现有感染和继发感染的反应。在本研究中，我们利用从白色念珠菌中分离的β-葡聚糖来 诱导训练有素的免疫力。β-葡聚糖试剂是在PIS(威廉姆斯)实验室制备的，它是免疫的 在ETSU(Williams)和Vanderbilt的家长奖中详细说明的实验所使用的培训试剂 (舍伍德)事实上，威廉姆斯实验室是β-葡聚糖免疫训练试剂的唯一来源，该试剂 受雇于家长奖。β-葡聚糖的分离和质量控制是一个多步骤的过程， 需要在制备级进行层析纯化，以获得高纯度，即&gt；95%，β- 在ETSU和Vanderbilt进行的实验所需的数量足够的葡聚糖试剂。我们的 目前的制备层析系统已有二十年的历史。它目前不能运行，必须 被替换了。本附录要求使用安捷伦1260 Infinity II制备层析系统。安捷伦 1260系统是一种高性能、全自动化的制备层析系统，具有多个 检测器，使我们能够分离和纯化足够数量的-葡聚糖，以便完成 我们父母奖的具体目标。

项目成果

Endothelial cell tolerance to lipopolysaccharide challenge is induced by monophosphoryl lipid A.

• DOI: 10.1042/cs20150592
• 发表时间: 2016-03
• 期刊: Clinical science (London, England : 1979)
• 作者: Stark RJ;Choi H;Koch SR;Fensterheim BA;Lamb FS;Sherwood ER
• 通讯作者: Sherwood ER

Flt3 Ligand Treatment Attenuates T Cell Dysfunction and Improves Survival in a Murine Model of Burn Wound Sepsis.

• DOI: 10.1097/shk.0000000000000688
• 发表时间: 2017-01
• 期刊: Shock (Augusta, Ga.)
• 作者: Patil NK;Bohannon JK;Luan L;Guo Y;Fensterheim B;Hernandez A;Wang J;Sherwood ER
• 通讯作者: Sherwood ER

Development of Negative Controls for Fc-C-Type Lectin Receptor Probes.

Fc-C 型凝集素受体探针阴性对照的开发。

• DOI: 10.1128/spectrum.01135-23
• 发表时间: 2023-06-15
• 期刊: MICROBIOLOGY SPECTRUM
• 影响因子: 3.7
• 作者: Hatinguais, Remi;Kay, Madalaine;Salazar, Fabian;Conn, Daniel P. P.;Williams, David L. L.;Cook, Peter C. C.;Willment, Janet A. A.;Brown, Gordon D. D.
• 通讯作者: Brown, Gordon D. D.

IL-15 Enables Septic Shock by Maintaining NK Cell Integrity and Function.

IL-15通过维持NK细胞完整性和功能来启用败血性休克。

• DOI: 10.4049/jimmunol.1601486
• 发表时间: 2017-02-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Guo Y;Luan L;Patil NK;Wang J;Bohannon JK;Rabacal W;Fensterheim BA;Hernandez A;Sherwood ER
• 通讯作者: Sherwood ER

The Cytokine Response to Lipopolysaccharide Does Not Predict the Host Response to Infection.

• DOI: 10.4049/jimmunol.1602106
• 发表时间: 2017-04-15
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Fensterheim BA;Guo Y;Sherwood ER;Bohannon JK
• 通讯作者: Bohannon JK